By Robert G. Bell
The search for novel drug products has researchers looking high and low for the next blockbuster. Recently, the search for novel antibiotics has led researchers to seek the latter. A previously unknown antibiotic, lactocillin, has been discovered from a vaginal commensal by a scientific consortium led by Michael Fischbach at the Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences at the University of California at San Francisco. An in silico learning algorithm program was designed by the research team to recognize genes that are already known to make small molecules that could act as drugs. When the program was queried to search for similar genes in the human microbiome, the program search yielded thousands of these drug-making genes within microbes living on and in the body. The researchers found over 3,000 small molecule gene clusters in the human microbiome, which may be a source for future drug discovery and development efforts. Furthermore, the researchers identified and purified lactocillin, which is a thiopeptide antibiotic from a prominent member of the vaginal microbiota, and demonstrated that lactocillin has potent antibacterial activity against a range of gram-positive vaginal pathogens. The researchers did not actually show that the human vaginal bacteria make the drug in the body, but they did demonstrate that the bacteria, with the appropriate bioprocessing, produces the lactocillinantibiotic.
“This is a great example of the power of bioinformatics to not merely identify genes of interest from ‘big data’ ‘omics, but to connect together cassettes of genes to increase our fundamental understanding of how commensal bacteria maintain a healthy human microbiome,” said microbial genomicist Derrick Fouts of the J. Craig Venter Institute in Rockville, MD. Rob Knight, a microbial ecologist at the University of Colorado, Boulder, stated, “This work provides an exciting platform for mining our microbiomes for new compounds of medical interest.”
The human body, internally and externally, contains numerous microorganisms that produce countless molecules and proteins which may lend themselves to drug development. Earlier this year, Pfizer announced plans to partner with Second Genome to study the microbiomes of hundreds of people with metabolic disorders as well as a control group for potential therapies. Fischbach indicated they do not plan to develop the lactocillin antibiotic into a drug, but rather elucidate additional novel types of molecules that are made by the microbiome.
So who knows next where the next big drug discovery may happen? Your lab or mine?